Therapeutic effect of pH responsive Magainin II modified azithromycin plus curcumin micelles in different depth models of MRSA infection.

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen responsible for serious infections in humans. The overuse of antibiotics has led to the evolution of resistance genes in bacteria. This study aimed to develop a pH-responsive micelle, loaded with therapy drugs and modified with antimicrobial peptides, to treat drug-resistant bacterial infections at varying depths. pH-responsive micelles containing azithromycin and curcumin, modified with Magainin II, were prepared using the thin-film dispersion method. The physicochemical properties of the micelles were characterized, and their targeting properties and therapeutic effects on bacterial infections were investigated both in vivo and in vitro across various depths. The micelles demonstrated excellent targeting of bacterial infection sites and released drugs in response to degradation at the disease site. The combination of curcumin and azithromycin effectively mitigated bacterial resistance through multiple mechanisms, enhancing the antibacterial effect while reducing the required azithromycin dosage and associated toxicity. In infection models of varying depths-skin, muscle, and lungs-the micelles exhibited strong antibacterial, anti-biofilm, and anti-inflammatory effects with low toxicity. These findings provide a promising strategy for addressing drug-resistant bacterial infections.